Prostate cancer is the most common cancer in men. About 30-40 thousand men will die of prostate cancer this year, most from metastatic disease. Recently, Sonic Hedgehog (Shh) signaling was implicated in the growth, invasiveness and metastasis of advanced prostate cancer. Shh and a second growth factor, FGF2, are expressed in metastatic prostate cancers. Signaling by these factors depends on heparan sulfate proteoglycans that regulate growth factor activity. A specific proteoglycan that modulates Shh signaling in advanced human prostate cancer cells has been identified. To examine the role of the proteoglycan in prostate cancer progression three aims are proposed: 1) Analysis of proteoglycan expression and function in Shh and FGF2 signaling in LNCaP cell lines of varying oncogenic and metastatic potential by Real Time PCR, immunoblots and knock-down technology. 2) Determination of the composition and modification of the heparan sulfate chains on the proteoglycan by HPLC and Mass Spectroscopy. 3) Evaluation of the role of proteoglycan function in invasiveness and metastasis using xenografts in immune compromised mice. These studies will link proteoglycan expression, signaling function and sugar structure to cancer progression.